tbuckley/cabot-search huggingface dataset:
Identification of a prognostic signature model for predicting disease-free survival of hepatocellular carcinoma.
Authors: Guangming Li, Huanhuan Liu, Daobing Zeng, Menglong Wang, Qingliang Guo, Jushan Wu, Zhi Fu, Haitao Zhang, Huina Wang
Journal: Journal of Clinical Oncology (2022)

e16128 Background: Hepatocellular carcinoma (HCC) is a type of aggressive disease with poor prognosis. Although surgery is the most effective therapy for early liver cancer, recurrence rate is up to 50%. Therefore, it is crucial to predict the recurrence for improvement of prognosis of liver cancer. This study aim is to establish a prognostic model using for the prediction of recurrence in HCC. Methods: We collected the genomic and clinical data of 372 patients from the cancer genome atlas (TCGA) database. Mutational signature were established based on univariate Cox analysis and least absolute shrinkage and selection operation (LASSO) Cox regression analysis. A prognostic signature model were developed. Results: The patients with higher pathological T stage (p &lt; 0.001) and old age (p = 0.05) were associated with a worse DFS. In addtion, patients with a HRD score over 24 had a worse DFS compared to those in patients with HRD score less than 24 (p &lt; 0.001). Based on the 1 year DFS, 112 differential mutation gene (DMEs) and 326 differential expressed genes (DEGs) were identified. The univariate Cox and LASSO Cox regression models were employed to select 47 DMEs and 9 gene expression construct an prognosis model. The AUC is 0.612. A nomogram of DFS was established based on the prognosis model, HRD, and tumor stage. The AUC is 0.812 in training set and 0.842 in validation set. Conclusions: We established and validated a novel nomogram model based the genomic and clinical factors for predict DFS in Hepatocellular Carcinoma patients. This model has good predictive value for prognosis, which could improve the risk stratification and individual treatment of Hepatocellular Carcinoma patients.
A randomized phase 2 study of continuous or intermittent dosing schedule of imatinib re-challenge in patients with tyrosine kinase inhibitor-refractory gastrointestinal stromal tumors.
Authors: Hyung-Don Kim, Changhoon Yoo, Min-Hee Ryu, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2022)

11538 Background: Resumption of imatinib is one of the available therapeutic options for patients with gastrointestinal stromal tumors (GIST) refractory to tyrosine kinase inhibitors (TKIs). Intermittent dosing of imatinib was suggested to delay outgrow of the imatinib-resistant clones in a preclinical study. Methods: A randomized phase 2 study was performed to evaluate the efficacy and safety of continuous or intermittent schedule of imatinib in GIST patients whose disease had progressed to at least imatinib and sunitinib. Patients were randomly assigned (1:1) to the intermittent dosing group that received 400mg daily imatinib based on a 1 week-on and 1 week-off schedule or the continuous dosing group that received imatinib 400mg daily without drug holiday. Disease control rate (DCR) rate at 12 weeks was the primary endpoint. Plasma samples were collected for circulating tumor DNA analysis at baseline, at 3 months of continuous or intermittent imatinib treatment and at the time of progressive disease. Results: Fifty patients received at least one dose of imatinib and were included in the full analysis set. Most patients (n = 46) had received prior regorafenib. DCR rate at 12 weeks was 34.8% and 43.5% in the continuous and intermittent groups, respectively. Median progression-free survival was 1.68 months and 1.57 months in the continuous and intermittent groups, respectively. The frequency of any grade anorexia, dysphagia, diarrhea, decreased neutrophil was lower in the intermittent group, whereas that of abdominal pain was higher in the intermittent group. Two patients in the continuous imatinib group underwent dose modification, and there was no patient who discontinued the study treatment because of adverse events related to study treatment. Conclusions: We confirmed that imatinib re-challenge was effective in TKI-refractory GIST patients. Intermittent dosing schedule may also be a clinically feasible treatment option for imatinib resumption in TKI-refractory GIST patients. Clinical trial information: NCT02712112.
Artificial intelligence algorithms for the diagnosis of urothelial carcinoma based on urine cytology: A noninvasive and efficient diagnostic approach.
Authors: Chong Shen, HaiTao Wang, Hailong Hu, Yuanjie Niu, Dawei Tian, Shiwang Huang, Gangjian Zhao, Chuanyi Huang, Zhouliang Wu, Zhe Zhang
Journal: Journal of Clinical Oncology (2022)

4590 Background: Urine cytology is a noninvasive and relatively inexpensive approach that plays an important role in both screening/initial diagnosis of urothelial carcinoma, and surveillance of tumor recurrence; However, interpretation of urine cytology is labor-intensive and time-consuming. Artificial intelligence (AI) has been widely used in the field of medically assisted diagnosis, but it is almost blank in the field of urothelial carcinoma diagnosis based on urine cytology. In this study, artificial intelligence (AI) algorithms have been developed to efficiently and automatically analyze urinary cytological specimens stained with Acridine orange fluorescence for screening and diagnosis of urothelial carcinoma with a good clinical application prospect. Methods: To develop the algorithms, images of urinary cytological specimens with Acridine orange Fluorescence staining were collected from patients who underwent examination, surgery, or both at the Second Hospital of Tianjin Medical University from August 2015 to August 2021. To standardize the urine cytological determination, the images were determined by 3 certified and experienced cytopathologists in this hospital. Images were collected to establish a dataset containing two major categories: Malignant (Defined as images containing malignant cells) and Benign (Defined as images containing malignant cells). From the acquired database, 2794 malignant and 2787 benign eligible images were selected for AI training/validation/testing. Inception V3, a specific type of neural network optimized for image classification called a deep convolutional neural network was trained based on the database. To prevent the model from over-fitting during training, data augmentation methods, such as rotation and flipping were adopted. The diagnosing performance of the binary classification model was analyzed using accuracy, F1 score, operating characteristic (ROC), and the area under the curve (AUC) generated from the sensitivity and specificity to evaluate. Results: A total of 21022 slides of urine cytological specimens with Acridine orange Fluorescence staining were collected. The AI algorithms achieved excellent performance, which showed the best prediction with an accuracy of 92.25%, a sensitivity of 98.50% along with a specificity of 86.00%, the F1score was 0.9271, and the area under the ROC curve was 0.96. Conclusions: Our novel artificial intelligence algorithms could accurately classify urine specimens as malignant or benign efficiently and automatically. The use of AI during cytopathology screening provides a new strategy and technical support for the diagnosis and screen of urothelial carcinoma. [Table: see text]
Sociodemographic factors associated with end-of-life palliative care utilization in female breast cancer: A national inpatient database analysis.
Authors: Tien-Chan Hsieh, Yuyao Wang, Guangchen Zou, Jiayi Zheng, Robert A. Kloss
Journal: Journal of Clinical Oncology (2022)

12035 Background: Palliative care (PC) has been shown to improve end-of-life quality in cancer patients. Nevertheless, several studies suggest that PC utilization is associated with socioeconomic factors. Patients with breast cancer, the most common neoplasm in women in the U.S., has lower PC utilization than those with other malignancies. We aim to investigate any sociodemographic barriers that are associated with the inpatient PC utilization in female breast cancer in the U.S. at the end of life. Methods: We used the National Inpatient Sample database of Healthcare Cost and Utilization Project, an all-payer inpatient care database in the United States, with data years 2014-2019. The end-of-life case was defined as hospitalized at least three days and passed away. We included all adult women (age at least 18 years old and female gender in electronic health records). The breast cancer cases were identified with International Classification of Diseases (ICD) 9th or 10th edition within the top three diagnoses. PC consultation could be identified with the ICD procedure code. Comorbidities were controlled with Charlson Comorbidity Index. After univariable analysis, the factors that were statistically associated with PC utilization would subsequently be added to the multivariable logistic regression model. Results: Between the year 2014 to 2019, we identified a total of 2,226 adult female patients who had breast cancer as their top three diagnoses and were hospitalized at least three days before death. 217 (9.7%) cases were 40-49 years old; 441 (19.8%) cases were 50-59 years old; and 1,455 (65.4%) patients were at least age 60 or above. The top three racial groups were Caucasian 1,420 (63.8%), African American 418 (18.8%), and Hispanic 166 (7.5%). 1,267 (56.9%) of all the cases had PC consult. African American (adjusted odds ratio [aOR]: 0.75; p &lt; 0.005) and Hispanic (aOR: 0.62; p &lt; 0.05) were significantly associated with less PC utilization than the Caucasian reference group in multivariable regression model. Lower PC prevalence was also observed at rural hospitals and Midwest region. Higher income group and private insurance no longer showed statistically significant higher PC utilization after adjusted for other variables. Conclusions: In end-of-life hospitalization with breast cancer as primary diagnosis, racial and hospital resource factors were significantly associated with the PC utilization. Cultural difference could be associated with the lower PC prevalence since adjusting income and insurance types could not explain the disparities in PC utilization among different racial groups. Future study should investigate and address the disparities of PC utilization in female terminal breast cancer.
Update to role of the neutrophil lymphocyte ratio in patients with advanced NSCLC undergoing immunotherapy.
Authors: Eduardo Richardet, Luciana Paola Acosta, Ignacio Magi, Rocio tello Alfonso, Rita Vanessa Peruchin, Pablo Perea, Matias Molina, Martin Richardet
Journal: Journal of Clinical Oncology (2022)

e21041 Background: The tumor microenvironment TME is a heterogeneous mixture of different tumor cells, necrotic cells and immune infíltrate.Furthermore nerves and vasculature immersed in the surrounding stroma. The TME cells have different immunological phenotypes. The infiltrating lymphocytes of the tumor stroma (tils) and neutrophil lymphocyte ratio (NLR) are a reflection of the state of “inflammation” in the TME and his systemic repercussion. In our institution we have carried out several research studies studying different markers of inflammation, such as BMI, TILs and NLR in different solid tumors. We conclude that these markers of inflammation have a role in tumor behavior, prognosis and response to treatment. The main objective was investigated the relationship between as NLR and progression-free survival (PFS).in patients with NSCLC who received immunotherapy. The secondary objective was to analyze if there is a relationship between ORR and NLR in patients with NSCLC. Methods: Retrospective and analytical study of patients of Instituto Oncológico de Córdoba. Patients with stage IV NSCLC were analyzed. Were included patient who performed IT alone or in combination with another immunomodulator or platinum-based chemotherapy. The cut-off value for NLR &gt; or &lt; 3 was taken. ORR was evaluated by RECIST criteria. For the statistical analysis of survival, Chi-Square test and Kaplan-Meyer test were used. Results: 52 pts with NSCLC were selected, the average age was 67 years. Of the total number of subjects analyzed, 75% (39) presented non-squamous histology and 25% (13) presented squamous histology. All performed IT (anti PD1) alone or in combination with another immunomodulator (Ipilimumab) or platinum-based CT. Of total patients analized, 27 pts had a NLR &lt; 3; and 25 pts NLR &gt; 3. The median overall survival (OS)was 8.5 months for general population. Patients with an NLR &lt; 3, the median PFS was 14.9 months and those with an NLR &gt; 3 was 5.5 months (p: 0.01). When analyzed the ORR in pts with NLR &lt; 3 it was 21% and those with NLR &gt; 3 the ORR was 4% with statistically significant differences (p:0.02). All patients had follow-up of at least 1 year4 patients (8%)with NLR &lt; 3 had disease progression at 6 months in differencies with patients with NLR &gt; 3 that had progression 13 pts (25%)(p:0.01) and these differences were maintained when we evaluated the PFS at year. Conclusions: Patients with NLR &lt; 3 had better progression-free survival and ORR. It is possible that NLR is a very useful and easily accessible predictive factor in patients with NSCLC undergoing immunotherapy.
A phase 1a dose-escalation study of PY314, a TREM2 (Triggering Receptor Expressed on Macrophages 2) targeting monoclonal antibody.
Authors: Amita Patnaik, Erika P. Hamilton, Ira Seth Winer, Winston Tan, Joleen M. Hubbard, Erin Lynn Schenk, Mohamad B. Sonbol, Nadine Jahchan, Kristen Pierce, Yunfeng Li, Len Reyno, Marc Chamberlain
Journal: Journal of Clinical Oncology (2022)

2648 Background: To characterize the safety and tolerability of PY314, an immunosuppressive macrophage depleting antibody, as a single agent and in combination with pembrolizumab in subjects with advanced refractory solid tumors including subject’s refractory to checkpoint inhibitors if approved for that indication. Methods: Two were evaluated in subjects with advanced solid tumors, single agent PY314 and PY314 in combination with 200 mg of pembrolizumab using a 3+3 dose escalation study design. Dosing was intravenous and administered once every 3-weeks, a defined cycle. Disease assessment by RECIST 1.1 was performed every 6 weeks. Each stratum included 4 dose levels of PY314 (1, 3, 10, and 20 mg/kg). Pharmacokinetics were evaluated at specified time points. Archival tumor tissue was analyzed for TREM2 expression by immunohistochemistry. Based on preclinical evaluation of TREM2 expression, HR+ HER2- and triple negative breast cancer, colorectal cancer, renal cell cancer, non-small cell lung cancer and gynecologic cancers were studied. Results: 28 subjects (median age 60 years [range 26-76], 22 females and 6 ) with an ECOG PS &lt;2 were enrolled and all, but one was (1 subject withdrew consent after dosing). 15 subjects were treated with single agent PY314 and 13 were treated with the combination. No infusion-related reactions, dose limiting toxicities, suspected unexpected serious adverse reactions or high-grade treatment related adverse events (TRAEs) that resulted in treatment discontinuance was seen. 12 subjects experienced at least one TRAE, and in all but one subject, these were low grade. One subject experienced a treatment-related immune system disorder. serious adverse events, all unrelated to treatment. TREM2 expression in archival tumor ranged from 0.0-20%. PY314 pharmacokinetics were linear, dose proportional, unaffected by concomitant pembrolizumab and with a half-life of 8-9 days. Best radiographic response was stable disease seen in 11 subjects (39.3%) ranging in duration from 9-42 weeks. 6 subjects with stable disease have progressed and 5 remain on treatment. Conclusions: PY314 was well tolerated and has an excellent safety profile both as a single agent and in combination with pembrolizumab. A recommended dose for expansion was derived and enrollment in five prespecified cancers is ongoing. Clinical trial information: 04691375.
Population-based retrospective analysis of response assessment criteria in patients with glioblastoma.
Authors: Parandoush Abbasian, Lawrence Ryner, Pascal Lambert, Anmol Mann, Jai Shankar, Marco Essig, Marshall W. Pitz
Journal: Journal of Clinical Oncology (2022)

2041 Background: Patients with glioblastoma are often treated with radiation and chemotherapy following surgery. Disease recurrence often occurs early in the disease course and during initial therapy, yet assessment of treatment response with MRI is highly variable in some situations. We sought to describe the clinical and imaging assessment and outcomes of an unselected cohort of patients with glioblastoma following the publication of the Response Assessment in Neuro-Oncology criteria. Methods: Patients diagnosed with glioblastoma in Manitoba, Canada, from 2012-2018 were identified from the Manitoba Cancer Registry. Chart review was performed to identify treatments given and decisions made by the treating team, and imaging analysis was performed to assess based on RANO and mRANO criteria. Determination of progression versus pseudoprogression according to these criteria was performed using clinical decision-making and review of follow-up imaging for confirmation. At time of the response assessment visit, patients were assessed by a primary oncologist (Radiation or Medical) and were also discussed at multidisciplinary Case Conference (comprised of Medical and Radiation Oncology, Neurosurgery, Neuropathology, and Neuroradiology). Treatment decisions were made with patient and primary oncologist, guided by input from the Case Conference. Tumour measurements were performed both in 2D using Product of Perpendicular Diameter analysis (PPD) and 3D volumetric measurements with/without necrotic region. Overall Survival (OS) and Progression Free Survival (PFS) were estimated to evaluate the effectiveness of response assessments and Kaplan-Meier method was used to compare the time to progression resulted from RANO, mRANO, and clinical impression. Results: A total of 285 patients were identified with a pathological diagnosis of glioblastoma. Of those, 199 (35% male, 65% female) were treated with concurrent temozolomide and radiation (75% 60Gy and 25% &lt; 60Gy), and more than 90% went on to receive adjuvant temozolomide. Median Overall Survival of the 199 was 13.2 months. Of those treated with concurrent therapy, 122 (61%) had MRI studies with equivocal results within the first 6 months, with confirmatory MRI showing true progression in 73 (59.8%), pseudoprogression in 45 (36.9%), and 4 patients with undetermined outcome. Formal RANO and mRANO comparison is ongoing. Conclusions: Response assessment for patients with glioblastoma remains a frequent challenge despite the use of MRI and established response criteria, with more than half of patients having equivocal imaging changes and a high frequency of pseudoprogression.
Diagnostic accuracy of the CxPREVENTIVE breast model for early detection of breast cancer.
Authors: Sergio J Calleja, Édgar C Patiño
Journal: Journal of Clinical Oncology (2022)

e13578 Background: Despite different available methods for breast cancer (BC) screening (mainly mammographies for ages between 50 and 65 yr.), and their proven benefits, morbidity, and mortality of this malignancy are still high, partly due to technical limitations and low compliance with screening. The aim of the present study was to assess the diagnostic accuracy for early detection of BC using a modeling algorithm based on multiple blood and urine biomarkers. Methods: In this retrospective cohort study, clinical and blood and urine markers-based algorithms with predefined cutoff values were applied to a generally healthy asymptomatic outpatient cohort of women aged 23 years or older undergoing mammography and histopathology for routine breast cancer screening. We used a modeling algorithm based on two different frameworks (Multiple Biomarkers Disease Activity Algorithm MBDAA [Bioprognos], and Artificial Intelligence Recursive Algorithm AIRA [Mintlot] both in Barcelona, Spain). Both algorithms compute information from a wide number of analytes, tumor markers (CA 15.3, CEA, EGFR, NGAL, NSE and 8-OHdG), and additional clinical data (age, weight, height, and BMI). MBDAA includes Barcelona Criteria (four criteria to correctly interpret the cause of the increase in tumor markers, benign or malignant, defined by the Spanish Society of Clinical Biochemistry and Molecular Pathology, Commission of Biological Markers of Cancer). To assess the association between the modelling algorithm and downstream diagnosis we used logistic regression to compute receiver operating characteristic curves (ROC). Exact binomial confidence limits were calculated to test accuracy, sensitivity, and specificity. Results: 123 women (median age 48 yr. [IQR 40-63]) who underwent mammography at the Juan Ramón Jiménez Hospital (Huelva, Spain), were included in this analysis. Based on mammography and histopathologic findings, BC was diagnosed in 61 (49.5%) women, and absence of pathological findings (control group) was seen in 62 (51.5%). The diagnostic intervention for BC yielded an area under the curve (AUC) of 1 among the entire specimen set, accuracy 1 (95% CI 0.990,1), Se 1 (0.991, 1) and Sp 1 (0.991, 1). Conclusions: Using mammography as a gold standard, our data suggest that an innovative newly designed non-invasive blood and urine-based biomarker algorithm CxPREVENTIVE Breast may provide a timely diagnosis of BC with very high accuracy, especially for those women under 50 and over 65yr., where up to 60% of all BC are concentrated. Our findings warrant further investigation, and we are planning large-scale (n 10,000), fully powered study to inform clinical practice.
Genomic correlates of response to capecitabine and temozolomide (CAPTEM) in pancreatic neuroendocrine tumors.
Authors: Patrick Lee, Edik Matthew Blais, Jun Gong, Arsen Osipov, Natalie Moshayedi, Shant Thomassian, Camille Ng, Jennifer W. Chuy, Lynn McCormick Matrisian, Emanuel Petricoin, Michael J. Pishvaian, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2022)

4124 Background: Despite the frequent use of capecitabine and temozolomide (CAPTEM) to treat metastatic, well-differentiated pancreatic neuroendocrine tumors (PNETs), no reliable genomic predictors of response currently exist. PNETs commonly harbor mutations in MEN1, ATRX, DAXX, and the PI3K/AKT/mTOR pathway. We sought to determine whether the mutational status of these genes correlates with response to CAPTEM. Methods: A retrospective cohort of PNET cases seen at Cedars-Sinai Medical Center or from Perthera’s Real-World Evidence Database included 23 patients who were treated with CAPTEM in 1 st or 2 nd line and had targeted next-generation sequencing (NGS) of their tumors available. Genomic alterations were correlated with progression-free survival (PFS) using multivariate Cox regression analysis. Results: We analyzed 23 PNET patients, 4 (17.4%) of whom had documented functional tumors. We identified MEN1 mutations as positively associated with CAPTEM response, but this effect was less pronounced for the subset with co-occurring DAXX mutations, which are commonly found alongside MEN1 alterations. With and without accounting for line of therapy, we found that PFS on CAPTEM was significantly longer in MEN1-mutated, DAXX-wildtype tumors compared to other mutation profiles ( P &lt; 0.01, see Table). ATRX (67%) and PTEN (33%) alterations were also enriched in the MEN1-mutated/ DAXX-wildtype subset; however, other PI3K/AKT/mTOR alterations were common across all MEN1-mutated cases. Conclusions: We describe a novel genomic signature ( MEN1 mut/ DAXX wt) that correlates with PNET response to CAPTEM therapy and is exploratory in nature. Prospective validation of these associations is warranted while taking into account other therapies, histopathologic factors, and other genomic correlates. [Table: see text]